Hyperactivity and tic symptoms in children and adolescents with Attention Deficit Hyperactivity Disorder(ADHD)have a bidirectional association with sleep disorders,while magnesium deficiency is a key nutritional facto...Hyperactivity and tic symptoms in children and adolescents with Attention Deficit Hyperactivity Disorder(ADHD)have a bidirectional association with sleep disorders,while magnesium deficiency is a key nutritional factor exacerbating this vicious cycle.The SLS Magnesium Glycinate Complex Liquid Supplement formula adopts the core logic of“sleep improvement-mood stabilization-behavioral regulation”and enhances the neuromodulatory effects of magnesium ions through multi-component synergy.Tailored to the developmental needs of different stages aged 4-16 years,the formula features a child-friendly dosage design,forming a closed-loop regulation in aiding sleep,reducing tics,and maintaining daytime functioning.A 3-month clinical trial showed that the formula improved sleep efficiency by 15%-23%,reduced tic frequency by 21%-32%,and enhanced emotional stability scores by 24%-30%across all age groups with ADHD,with good safety and tolerability.This study provides a targeted nutritional intervention solution for ADHD,and its age-stratified design concept offers scientific reference for precise nutritional support during different developmental stages of children and adolescents.展开更多
Solar-driven photocatalysis with charge-transfer modulation is a green approach for enhancing the oxygen reduction reaction(ORR)to generate hydrogen peroxide(H_(2)O_(2)).In this study,we introduced a novel method for ...Solar-driven photocatalysis with charge-transfer modulation is a green approach for enhancing the oxygen reduction reaction(ORR)to generate hydrogen peroxide(H_(2)O_(2)).In this study,we introduced a novel method for synthesizing high-valence Sn^(δ+)in SnS_(2),combined with gC_(3)N_(4)to create gC_(3)N_(4)/SnS_(2).Density functional theory(DFT)calculations exhibited that the interface between SnS_(2)and gC_(3)N_(4)creates interband states through strong hybridization,revealing that photoexcited electrons flowed from C in gC_(3)N_(4)to S in SnS_(2),forming a Z-scheme heterojunction.The optimal gC_(3)N_(4)/SnS_(2)-2(2%SnS_(2)loaded)achieved a high H_(2)O_(2)production rate of 7.186 mmol g^(-1)h^(-1)and an apparent quantum efficiency(AQE)of 33.8%at 405 nm with isopropanol(IPA),converting 88.8%IPA to acetone in 2 h.The gC_(3)N_(4)/SnS_(2)composite improved the charge transfer resistance and elongated the non-radiative electron decay time.Notably,SnS_(2)doping of gC_(3)N_(4)decreased the antibonding orbital occupancy and lowered the energy barrier for O_(2) and OOH^(*)adsorption.In situ surface-enhanced Raman spectroscopy(SERS)analysis confirmed the generation of OOH^(*)on gC_(3)N_(4)/SnS_(2)during light irradiation.A techno-economic analysis(TEA)was conducted to evaluate the economic viability of photocatalytic H_(2)O_(2)production,revealing that it was not economically feasible owing to challenges in the separation process.This study provides unique perspectives on the approaches to inducing a high valence state of Sn^(δ+)for enhancing photocatalytic H_(2)O_(2)generation and the challenge of commercializing H_(2)O_(2)production via photocatalysis.展开更多
Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the...Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.展开更多
The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore p...The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore potential therapeutic interventions.Although promising therapeutics have been identified using these animal models,with most undergoing significant testing in rodent models,the vast majority of these interventions have failed in human clinical trials.This failure of preclinical translation highlights the critical need for better therapeutic assessment in more clinically relevant ischemic stroke animal models.Large animal models such as non-human primates,sheep,pigs,and dogs are likely more predictive of human responses and outcomes due to brain anatomy and physiology that are more similar to humans-potentially making large animal testing a key step in the stroke therapy translational pipeline.The objective of this review is to highlight key characteristics that potentially make these gyrencephalic,large animal ischemic stroke models more predictive by comparing pathophysiological responses,tissue-level changes,and model limitations.展开更多
Vision is an ability that depends on the precise structure and functioning of the retina.Any kind of stress or injury can disrupt the retinal architecture and leads to vision impairment,vision loss,and blindness.Immun...Vision is an ability that depends on the precise structure and functioning of the retina.Any kind of stress or injury can disrupt the retinal architecture and leads to vision impairment,vision loss,and blindness.Immune system and immune response function maintain homeostasis in the microenvironment.Several genetic,metabolic,and environmental factors may alter retinal homeostasis,and these events may initiate various inflammatory cascades.The prolonged inflammatory state may contribute to the initiation and development of retinal disorders such as glaucoma,age-related macular degeneration,diabetic retinopathy,and retinitis pigmentosa,which pose a threat to vision.In the current review,we attempted to provide sufficient evidence on the role of inflammation in these retinal disorders.Moreover,this review paves the way to focus on therapeutic targets of the disease,which are found to be promising.展开更多
Colorectal cancer(CRC)is the third most diagnosed cancer and the second leading cause of cancer-related mortality in the United States.Across the globe,people in the age group older than 50 are at a higher risk of CRC...Colorectal cancer(CRC)is the third most diagnosed cancer and the second leading cause of cancer-related mortality in the United States.Across the globe,people in the age group older than 50 are at a higher risk of CRC.Genetic and environmental risk factors play a significant role in the development of CRC.If detected early,CRC is preventable and treatable.Currently,available screening methods and therapies for CRC treatment reduce the incidence rate among the population,but the micrometastasis of cancer may lead to recurrence.Therefore,the challenge is to develop an alternative therapy to overcome this complication.Nanotechnology plays a vital role in cancer treatment and offers targeted chemotherapies directly and selectively to cancer cells,with enhanced therapeutic efficacy.Additionally,nanotechnology elevates the chances of patient survival in comparison to traditional chemotherapies.The potential of nanoparticles includes that they may be used simultaneously for diagnosis and treatment.These exciting properties of nanoparticles have enticed researchers worldwide to unveil their use in early CRC detection and as effective treatment.This review discusses contemporary methods of CRC screening and therapies for CRC treatment,while the primary focus is on the theranostic approach of nanotechnology in CRC treatment and its prospects.In addition,this review aims to provide knowledge on the advancement of nanotechnology in CRC and as a starting point for researchers to think about new therapeutic approaches using nanotechnology.展开更多
Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet...Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet containing high methionine and low vitamins can lead to memory impairment by increasing global DNA methylation and therefore,silencing the netrin-1 gene,which encodes the glycoprotein involved in neurogenesis,axonal guidance and maintenance of the synaptic plasticity.Wild type(C57 BL/6 J) mice were fed with a diet containing excess methionine(1.2%),low-folate(0.08 mg/kg),vitamin B_6(0.01 mg/kg),and B_(12)(10.4 mg/kg) for 6 weeks.Mice were examined weekly for the long-term memory function,using a passive avoidance test,which determined loss of fear-motivated long-term memory starting from the fourth week of diet.Similarly,an increase in brain %5-methyl cytosine was observed starting from the 4 th week of diet in mice.Mice fed with a high methionine,low folate and vitamins containing diet showed a decrease in netrin-1 protein expression and an increase in netrin-1 gene promotor methylation,as determined by methylation-sensitive restriction enzyme-polymerase chain reaction analysis.The increase in methylation of netrin-1 gene was validated by high-resolution melting and sequencing analysis.Furthermore,the association of netrin-1 with memory was established by administering netrin that considerably restored long-term fear motivated memory.Taken together,these results suggest that a diet rich in methionine and lacking in folate and vitamin B_6/B_(12) can induce defects in learning and memory.Furthermore,the data indicates that decrease in netrin-1 expression due to hyper-methylation of its gene can be associated with memory loss.The animal procedures were approved by the Institutional Animal Care and Use Committee,University of Louisville,USA(No.A3586-01) on February 2,2018.展开更多
Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments;ho...Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments;however, identification of specific magnetic resonance imaging(MRI) biomarkers that are most reflective of injury severity and functional prognosis remain elusive. Therefore, the objective of this study was to utilize advanced statistical approaches to identify clinically relevant MRI biomarkers and predict functional outcomes using MRI metrics in a translational large animal piglet TBI model. TBI was induced via controlled cortical impact and multiparametric MRI was performed at 24 hours and 12 weeks post-TBI using T1-weighted, T2-weighted, T2-weighted fluid attenuated inversion recovery, diffusion-weighted imaging, and diffusion tensor imaging. Changes in spatiotemporal gait parameters were also assessed using an automated gait mat at 24 hours and 12 weeks post-TBI. Principal component analysis was performed to determine the MRI metrics and spatiotemporal gait parameters that explain the largest sources of variation within the datasets. We found that linear combinations of lesion size and midline shift acquired using T2-weighted imaging explained most of the variability of the data at both 24 hours and 12 weeks post-TBI. In addition, linear combinations of velocity, cadence, and stride length were found to explain most of the gait data variability at 24 hours and 12 weeks post-TBI. Linear regression analysis was performed to determine if MRI metrics are predictive of changes in gait. We found that both lesion size and midline shift are significantly correlated with decreases in stride and step length. These results from this study provide an important first step at identifying relevant MRI and functional biomarkers that are predictive of functional outcomes in a clinically relevant piglet TBI model. This study was approved by the University of Georgia Institutional Animal Care and Use Committee(AUP: A2015 11-001) on December 22, 2015.展开更多
The largest superfamily Entomobryoidea is one of the key groups in Collembola.However,incorrect recognition of chaetotaxic homology within Entomobryoidea severely impedes the accurate species comparison of adults and ...The largest superfamily Entomobryoidea is one of the key groups in Collembola.However,incorrect recognition of chaetotaxic homology within Entomobryoidea severely impedes the accurate species comparison of adults and phylogenetic reconstruction.Traditional classification of the superfamily at suprageneric level is disputable in the light of recent advances.Transformational homology of tergal chaetotaxy was traced and revised based on 38 species of first instar and partial early instars.Morphological phylogenetic reconstructions were reconstructed mainly relying on first instar characters using both parsimony and likelihoodbased algorithms.Outgroup selection and several rogue taxa impacted on resolution and support of otherwise well-supported clades.Integrating published molecular phylogeny,a revised classification of three families and nine subfamilies was presented:Orchesellidae,Entomobryidae and Paronellidae.Orchesellidae includes all basal taxa having a short fourth abdominal segment.Cyphoderidae and Microfalculidae taxa were sunk into Paronellidae.New Paronellidae was divided into two subfamilies:Paronellinae(Paronellini+Cyphoderini+Bromacanthini)and Salininae(Cremastocephalini+Callyntrurini).Microfalculidae(Microfalcula)was closer to Salina and Akabosia and thus transferred into Cremastocephalini.This study erected a new classification framework for Entomobryoidea based upon comprehensive phylogenies.Chaetotaxic homologization across a wide range provided a standardized,comparable,powerful tool for taxonomy.展开更多
Male meiosis is a complex process whereby spermatocytes undergo cell division to form haploid cells.This review focuses on the role of retinoic acid(RA)in meiosis,as well as several processes regulated by RA before ce...Male meiosis is a complex process whereby spermatocytes undergo cell division to form haploid cells.This review focuses on the role of retinoic acid(RA)in meiosis,as well as several processes regulated by RA before cell entry into meiosis that are critical for proper meiotic entry and completion.Here,we discuss RA metabolism in the testis as well as the roles of stimulated by retinoic acid gene 8(STRA8)and MEIOSIN,which are responsive to RA and are critical for meiosis.We assert that transcriptional regulation in the spermatogonia is critical for successful meiosis.展开更多
BACKGROUND This study aimed to explore clinical and molecular factors that cause discordance for clinical expression of Leber’s hereditary optic neuropathy(LHON)in a pair of identical twins with the 14484 point mutat...BACKGROUND This study aimed to explore clinical and molecular factors that cause discordance for clinical expression of Leber’s hereditary optic neuropathy(LHON)in a pair of identical twins with the 14484 point mutation.CASE SUMMARY Twin patients with the 14484 point mutation were studied for zygosity by using the Short Tandem Repeats Typing system.For the monozygotic twins,the radioactive restriction and densitometric analyses were used to quantitate the heteroplasmy level for the 14484 point mutation.The mitochondrial genome was analyzed to determine influential factors by mitochondrial deoxyribonucleic acid(DNA)sequencing,denaturing high-performance liquid chromatography and next generation sequencing.For the dizygotic twins,the nuclear DNA was analyzed.The twins with 14484 LHON were monozygotic with homoplasmy.No difference in the point mutation in mitochondrial DNA was found.No modifying genes that potentially influenced the disparity in phenotypic expression of LHON were detected in these twins.CONCLUSION This 11-year follow-up of monozygotic twins showed additional genetic modifications and epigenetic factors are possibly associated with discordance for LHON.展开更多
The measurement of atmospheric O_(2)concentrations and related oxygen budget have been used to estimate terrestrial and oceanic carbon uptake.However,a discrepancy remains in assessments of O_(2)exchange between ocean...The measurement of atmospheric O_(2)concentrations and related oxygen budget have been used to estimate terrestrial and oceanic carbon uptake.However,a discrepancy remains in assessments of O_(2)exchange between ocean and atmosphere(i.e.air-sea O_(2)flux),which is one of the major contributors to uncertainties in the O_(2)-based estimations of the carbon uptake.Here,we explore the variability of air-sea O_(2)flux with the use of outputs from Coupled Model Intercomparison Project phase 6(CMIP6).The simulated air-sea O_(2)flux exhibits an obvious warming-induced upward trend(~1.49 Tmol yr−2)since the mid-1980s,accompanied by a strong decadal variability dominated by oceanic climate modes.We subsequently revise the O_(2)-based carbon uptakes in response to this changing air-sea O_(2)flux.Our results show that,for the 1990−2000 period,the averaged net ocean and land sinks are 2.10±0.43 and 1.14±0.52 GtC yr−1 respectively,overall consistent with estimates derived by the Global Carbon Project(GCP).An enhanced carbon uptake is found in both land and ocean after year 2000,reflecting the modification of carbon cycle under human activities.Results derived from CMIP5 simulations also investigated in the study allow for comparisons from which we can see the vital importance of oxygen dataset on carbon uptake estimations.展开更多
Chemical modification of penicillin β-lactam ring was made.Six thiazolidine amides were produced through N4-C7 β-lactam ring opening of penicillin V methyl ester with various aliphatic,aromatic,and heterocyclic prim...Chemical modification of penicillin β-lactam ring was made.Six thiazolidine amides were produced through N4-C7 β-lactam ring opening of penicillin V methyl ester with various aliphatic,aromatic,and heterocyclic primary amines.Five 8-hydroxypenillic acid derivatives with side chains of methyl,propyl,benzyl,and diethylaminoethyl groups were yielded via β-lactam ring rearrangement from6-aminopenicillanic acid(6-APA).Parallel synthetic methods were used for the alkylation of8-hydroxypenillic acid and β-lactam ring opening of penicillin V methyl ester.The biological activities of the compounds were evaluated.展开更多
Magnetic resonance imaging(MRI)is a clinically relevant,real-time imaging modality that is frequently utilized to assess stroke type and severity.However,specific MRI biomarkers that can be used to predict long-term f...Magnetic resonance imaging(MRI)is a clinically relevant,real-time imaging modality that is frequently utilized to assess stroke type and severity.However,specific MRI biomarkers that can be used to predict long-term functional recovery are still a critical need.Consequently,the present study sought to examine the prognostic value of commonly utilized MRI parameters to predict functional outcomes in a porcine model of ischemic stroke.Stroke was induced via permanent middle cerebral artery occlusion.At 24 hours post-stroke,MRI analysis revealed focal ischemic lesions,decreased diffusivity,hemispheric swelling,and white matter degradation.Functional deficits including behavioral abnormalities in open field and novel object exploration as well as spatiotemporal gait impairments were observed at 4 weeks post-stroke.Gaussian graphical models identified specific MRI outputs and functional recovery variables,including white matter integrity and gait performance,that exhibited strong conditional dependencies.Canonical correlation analysis revealed a prognostic relationship between lesion volume and white matter integrity and novel object exploration and gait performance.Consequently,these analyses may also have the potential of predicting patient recovery at chronic time points as pigs and humans share many anatomical similarities(e.g.,white matter composition)that have proven to be critical in ischemic stroke pathophysiology.The study was approved by the University of Georgia(UGA)Institutional Animal Care and Use Committee(IACUC;Protocol Number:A2014-07-021-Y3-A11 and 2018-01-029-Y1-A5)on November 22,2017.展开更多
Enterococcus faecalis is a Gram-positive bacterium commonly found in the gastrointestinal tract that can cause serious infections. Many enterococci have broad resistance to antibiotics including penicillin, cephalospo...Enterococcus faecalis is a Gram-positive bacterium commonly found in the gastrointestinal tract that can cause serious infections. Many enterococci have broad resistance to antibiotics including penicillin, cephalosporins, aminoglycosides and glycopeptides. There are several adaptation mechanisms that bacteria can undergo to become more resistant, among them is the formation of biofilm. Several genes have been linked to the increase in the capacity of biofilm formation by bacteria such as gelE, esp and asa1. The aim of this research was to evaluate the biofilm formation of 12 E. faecalis isolates collected in hospitals and a standard strain, as well as to evaluate the hydrophobicity of its membrane and the presence of virulence genes. All the isolates formed biofilm and the characteristics of their membrane were variable. In addition, the presence of at least one virulence gene was found in all the 12 isolates, and none of the genes in the standard strain, indicating the acquisition of these genes in the hospital environment. With this, we can conclude that there is a close relationship between biofilm formation, acquisition of antibiotic resistance and the presence of virulence genes.展开更多
Background: Postzygotic isolation in the form of reduced viability and/or fertility of hybrids may help maintain species boundaries in the face of interspecific gene flow. Past hybridization events between house sparr...Background: Postzygotic isolation in the form of reduced viability and/or fertility of hybrids may help maintain species boundaries in the face of interspecific gene flow. Past hybridization events between house sparrows(Passer domesticus) and Spanish sparrows(P. hispaniolensis) have given rise to a homoploid hybrid species, the Italian sparrow(P. italiae). Although genetic incompatibilities are known to isolate these three species, the biological consequences of these incompatibilities are still unknown in early generation hybrids.Methods: We investigated whether F1 hybrids between house and Spanish sparrows experience reduced viability or fertility. More specifically, we generated hybrids through controlled crosses in aviaries, and compared ovaries of female hybrids with female of pure?species sparrows.Results: We found that overall, hybrid ovaries were underdeveloped and that half of all female hybrids exhibited symptoms of ovarian hypofunction(ovarian atrophy and complete absence of developed follicles).Conclusions: Fertility in hybrids is a common consequence or post?zygotic barriers between species. We discuss these results in light of previous findings on genetic incompatibilities between the parent species and the potential role of incompatibilities in hybrid speciation, a rare evolutionary process in birds.展开更多
The influence of pollution from petroleum refining activities on the levels of nitrates and nitrites in five edible vegetable species was investigated. Besides, the kinetics of nitrite and nitrate was studied in vivo ...The influence of pollution from petroleum refining activities on the levels of nitrates and nitrites in five edible vegetable species was investigated. Besides, the kinetics of nitrite and nitrate was studied in vivo using albino rats with focus on the possible influence of concentration difference on kinetics and implications to toxicity. Leaf samples of the five vegetable species were collected randomly from various locations within Eleme, a host community of Port Harcourt Refinery Company and the Indorama Petrochemical Company. Also, samples were collected from Umuahia, which served as pollution-free control. The leaf samples were analyzed for their nitrite and nitrate contents. Nitrite was determined spectrophotometrically while nitrate was determined after cadmium column reduction. Results showed that samples from Eleme had higher mean nitrate (349.20 mg/100g dry leaf mass;P 0.05) as compared to the same samples from Umuahia. Solutions of nitrate and nitrite, equivalent in concentration to mean nitrate and nitrite content of the vegetable samples from the two locations were administered enterally to four groups of albino rats. Analysis of their blood levels were monitored five times at 30 minutes intervals following administration. Rates of change of blood nitrites and nitrates were found to be fairly constant in absorption as well as in the elimination phase. Their peak blood concentrations varied proportionately with their concentrations in administered solutions. However, peak blood nitrate was attained later in group of animals receiving higher amount of nitrate solution. Refining activities may pre-dispose people living within Eleme community to health hazards through contamination of edible vegetables.展开更多
Lentiviral vectors have drawn considerable attention recently and show great promise to become important delivery vehicles for future gene transfer manipulation. In the present study we have optimized a protocol for p...Lentiviral vectors have drawn considerable attention recently and show great promise to become important delivery vehicles for future gene transfer manipulation. In the present study we have optimized a protocol for preparation of human immunodeficiency virus type-1 (HIV-1)-based defective lentiviral vectors (DLV) and characterized these vectors in terms of their transduction of different cells. Transient co-transfection of 293T packaging cells with DNA plasmids encoding lentiviral vector constituents resulted in production of high-titer DLV (0.5-1.2 × 107IU/mL), which can be further concentrated over 100-fold through a single step ultracentrifugation. These vectors were capable of transducing a variety of cells from both primate and non-primate sources and high transduction efficiency was achieved using concentrated vectors. Assessment of potential generation of RCV revealed no detection of infection by infectious particles in DLV-transduced CEM, SupT-1 and MT-2 cells. Long-term culture of transduced cells showed a stable expression of transgenes without apparent alteration in cellular morphology and growth kinetics. Vector mobilization to untransduced cells mediated by wild-type HIV-1 infection was confirmed in this test. Challenge of transduced human T-lymphocytes with wild-type HIV-1 showed these cells are totally resistant to the viral infection. Considering the effective gene transfer and stable gene expression, safety and anti-HIV activity, these DLV vectors warrant further exploration for their potential use as a gene transfer vehicle in the development of gene therapy protocols.展开更多
文摘Hyperactivity and tic symptoms in children and adolescents with Attention Deficit Hyperactivity Disorder(ADHD)have a bidirectional association with sleep disorders,while magnesium deficiency is a key nutritional factor exacerbating this vicious cycle.The SLS Magnesium Glycinate Complex Liquid Supplement formula adopts the core logic of“sleep improvement-mood stabilization-behavioral regulation”and enhances the neuromodulatory effects of magnesium ions through multi-component synergy.Tailored to the developmental needs of different stages aged 4-16 years,the formula features a child-friendly dosage design,forming a closed-loop regulation in aiding sleep,reducing tics,and maintaining daytime functioning.A 3-month clinical trial showed that the formula improved sleep efficiency by 15%-23%,reduced tic frequency by 21%-32%,and enhanced emotional stability scores by 24%-30%across all age groups with ADHD,with good safety and tolerability.This study provides a targeted nutritional intervention solution for ADHD,and its age-stratified design concept offers scientific reference for precise nutritional support during different developmental stages of children and adolescents.
基金supported by the National Research Foundation of South Korea(NRF)grant funded by the Korean government(Grant No.2021R1A6A1A03038785,2023R1A2C1003464,RS-2024-00512818 and RS-2023-00240726)。
文摘Solar-driven photocatalysis with charge-transfer modulation is a green approach for enhancing the oxygen reduction reaction(ORR)to generate hydrogen peroxide(H_(2)O_(2)).In this study,we introduced a novel method for synthesizing high-valence Sn^(δ+)in SnS_(2),combined with gC_(3)N_(4)to create gC_(3)N_(4)/SnS_(2).Density functional theory(DFT)calculations exhibited that the interface between SnS_(2)and gC_(3)N_(4)creates interband states through strong hybridization,revealing that photoexcited electrons flowed from C in gC_(3)N_(4)to S in SnS_(2),forming a Z-scheme heterojunction.The optimal gC_(3)N_(4)/SnS_(2)-2(2%SnS_(2)loaded)achieved a high H_(2)O_(2)production rate of 7.186 mmol g^(-1)h^(-1)and an apparent quantum efficiency(AQE)of 33.8%at 405 nm with isopropanol(IPA),converting 88.8%IPA to acetone in 2 h.The gC_(3)N_(4)/SnS_(2)composite improved the charge transfer resistance and elongated the non-radiative electron decay time.Notably,SnS_(2)doping of gC_(3)N_(4)decreased the antibonding orbital occupancy and lowered the energy barrier for O_(2) and OOH^(*)adsorption.In situ surface-enhanced Raman spectroscopy(SERS)analysis confirmed the generation of OOH^(*)on gC_(3)N_(4)/SnS_(2)during light irradiation.A techno-economic analysis(TEA)was conducted to evaluate the economic viability of photocatalytic H_(2)O_(2)production,revealing that it was not economically feasible owing to challenges in the separation process.This study provides unique perspectives on the approaches to inducing a high valence state of Sn^(δ+)for enhancing photocatalytic H_(2)O_(2)generation and the challenge of commercializing H_(2)O_(2)production via photocatalysis.
文摘Traumatic brain injury(TBI) is a major contributor of long-term disability and a leading cause of death worldwide. A series of secondary injury cascades can contribute to cell death, tissue loss, and ultimately to the development of functional impairments. However, there are currently no effective therapeutic interventions that improve brain outcomes following TBI. As a result, a number of experimental TBI models have been developed to recapitulate TBI injury mechanisms and to test the efficacy of potential therapeutics. The pig model has recently come to the forefront as the pig brain is closer in size, structure, and composition to the human brain compared to traditional rodent models, making it an ideal large animal model to study TBI pathophysiology and functional outcomes. This review will focus on the shared characteristics between humans and pigs that make them ideal for modeling TBI and will review the three most common pig TBI models–the diffuse axonal injury, the controlled cortical impact, and the fluid percussion models. It will also review current advances in functional outcome assessment measures and other non-invasive, translational TBI detection and measurement tools like biomarker analysis and magnetic resonance imaging. The use of pigs as TBI models and the continued development and improvement of translational assessment modalities have made significant contributions to unraveling the complex cascade of TBI sequela and provide an important means to study potential clinically relevant therapeutic interventions.
基金supported by the National Institutes of Health,National Institute of Neurological Disorders and Stroke,No.R01NS093314
文摘The high morbidity and mortality rate of ischemic stroke in humans has led to the development of numerous animal models that replicate human stroke to further understand the underlying pathophysiology and to explore potential therapeutic interventions.Although promising therapeutics have been identified using these animal models,with most undergoing significant testing in rodent models,the vast majority of these interventions have failed in human clinical trials.This failure of preclinical translation highlights the critical need for better therapeutic assessment in more clinically relevant ischemic stroke animal models.Large animal models such as non-human primates,sheep,pigs,and dogs are likely more predictive of human responses and outcomes due to brain anatomy and physiology that are more similar to humans-potentially making large animal testing a key step in the stroke therapy translational pipeline.The objective of this review is to highlight key characteristics that potentially make these gyrencephalic,large animal ischemic stroke models more predictive by comparing pathophysiological responses,tissue-level changes,and model limitations.
基金supported by a National Institutes of Health grant,EY029709(to NKS)a Research to Prevent Blindness unrestricted grant to Kresge Eye Instituteby P30EY04068(LDH)at Wayne State University(to NKS)。
文摘Vision is an ability that depends on the precise structure and functioning of the retina.Any kind of stress or injury can disrupt the retinal architecture and leads to vision impairment,vision loss,and blindness.Immune system and immune response function maintain homeostasis in the microenvironment.Several genetic,metabolic,and environmental factors may alter retinal homeostasis,and these events may initiate various inflammatory cascades.The prolonged inflammatory state may contribute to the initiation and development of retinal disorders such as glaucoma,age-related macular degeneration,diabetic retinopathy,and retinitis pigmentosa,which pose a threat to vision.In the current review,we attempted to provide sufficient evidence on the role of inflammation in these retinal disorders.Moreover,this review paves the way to focus on therapeutic targets of the disease,which are found to be promising.
基金Supported by the National Institutes of Health grant,R01EY029709
文摘Colorectal cancer(CRC)is the third most diagnosed cancer and the second leading cause of cancer-related mortality in the United States.Across the globe,people in the age group older than 50 are at a higher risk of CRC.Genetic and environmental risk factors play a significant role in the development of CRC.If detected early,CRC is preventable and treatable.Currently,available screening methods and therapies for CRC treatment reduce the incidence rate among the population,but the micrometastasis of cancer may lead to recurrence.Therefore,the challenge is to develop an alternative therapy to overcome this complication.Nanotechnology plays a vital role in cancer treatment and offers targeted chemotherapies directly and selectively to cancer cells,with enhanced therapeutic efficacy.Additionally,nanotechnology elevates the chances of patient survival in comparison to traditional chemotherapies.The potential of nanoparticles includes that they may be used simultaneously for diagnosis and treatment.These exciting properties of nanoparticles have enticed researchers worldwide to unveil their use in early CRC detection and as effective treatment.This review discusses contemporary methods of CRC screening and therapies for CRC treatment,while the primary focus is on the theranostic approach of nanotechnology in CRC treatment and its prospects.In addition,this review aims to provide knowledge on the advancement of nanotechnology in CRC and as a starting point for researchers to think about new therapeutic approaches using nanotechnology.
文摘Memory-epigenetics which is the loss of memory due to epigenetic modifications can be due to the silencing of genes involved in cognitive functions and this is the basis of the current study.We hypothesize that a diet containing high methionine and low vitamins can lead to memory impairment by increasing global DNA methylation and therefore,silencing the netrin-1 gene,which encodes the glycoprotein involved in neurogenesis,axonal guidance and maintenance of the synaptic plasticity.Wild type(C57 BL/6 J) mice were fed with a diet containing excess methionine(1.2%),low-folate(0.08 mg/kg),vitamin B_6(0.01 mg/kg),and B_(12)(10.4 mg/kg) for 6 weeks.Mice were examined weekly for the long-term memory function,using a passive avoidance test,which determined loss of fear-motivated long-term memory starting from the fourth week of diet.Similarly,an increase in brain %5-methyl cytosine was observed starting from the 4 th week of diet in mice.Mice fed with a high methionine,low folate and vitamins containing diet showed a decrease in netrin-1 protein expression and an increase in netrin-1 gene promotor methylation,as determined by methylation-sensitive restriction enzyme-polymerase chain reaction analysis.The increase in methylation of netrin-1 gene was validated by high-resolution melting and sequencing analysis.Furthermore,the association of netrin-1 with memory was established by administering netrin that considerably restored long-term fear motivated memory.Taken together,these results suggest that a diet rich in methionine and lacking in folate and vitamin B_6/B_(12) can induce defects in learning and memory.Furthermore,the data indicates that decrease in netrin-1 expression due to hyper-methylation of its gene can be associated with memory loss.The animal procedures were approved by the Institutional Animal Care and Use Committee,University of Louisville,USA(No.A3586-01) on February 2,2018.
基金Financial support was provided by the University of Georgia Office of the Vice President for Research to FDW。
文摘Traumatic brain injury(TBI) at a young age can lead to the development of long-term functional impairments. Severity of injury is well demonstrated to have a strong influence on the extent of functional impairments;however, identification of specific magnetic resonance imaging(MRI) biomarkers that are most reflective of injury severity and functional prognosis remain elusive. Therefore, the objective of this study was to utilize advanced statistical approaches to identify clinically relevant MRI biomarkers and predict functional outcomes using MRI metrics in a translational large animal piglet TBI model. TBI was induced via controlled cortical impact and multiparametric MRI was performed at 24 hours and 12 weeks post-TBI using T1-weighted, T2-weighted, T2-weighted fluid attenuated inversion recovery, diffusion-weighted imaging, and diffusion tensor imaging. Changes in spatiotemporal gait parameters were also assessed using an automated gait mat at 24 hours and 12 weeks post-TBI. Principal component analysis was performed to determine the MRI metrics and spatiotemporal gait parameters that explain the largest sources of variation within the datasets. We found that linear combinations of lesion size and midline shift acquired using T2-weighted imaging explained most of the variability of the data at both 24 hours and 12 weeks post-TBI. In addition, linear combinations of velocity, cadence, and stride length were found to explain most of the gait data variability at 24 hours and 12 weeks post-TBI. Linear regression analysis was performed to determine if MRI metrics are predictive of changes in gait. We found that both lesion size and midline shift are significantly correlated with decreases in stride and step length. These results from this study provide an important first step at identifying relevant MRI and functional biomarkers that are predictive of functional outcomes in a clinically relevant piglet TBI model. This study was approved by the University of Georgia Institutional Animal Care and Use Committee(AUP: A2015 11-001) on December 22, 2015.
基金supported by the National Natural Science Foundation of China(31772491,31970434) to Feng Zhang
文摘The largest superfamily Entomobryoidea is one of the key groups in Collembola.However,incorrect recognition of chaetotaxic homology within Entomobryoidea severely impedes the accurate species comparison of adults and phylogenetic reconstruction.Traditional classification of the superfamily at suprageneric level is disputable in the light of recent advances.Transformational homology of tergal chaetotaxy was traced and revised based on 38 species of first instar and partial early instars.Morphological phylogenetic reconstructions were reconstructed mainly relying on first instar characters using both parsimony and likelihoodbased algorithms.Outgroup selection and several rogue taxa impacted on resolution and support of otherwise well-supported clades.Integrating published molecular phylogeny,a revised classification of three families and nine subfamilies was presented:Orchesellidae,Entomobryidae and Paronellidae.Orchesellidae includes all basal taxa having a short fourth abdominal segment.Cyphoderidae and Microfalculidae taxa were sunk into Paronellidae.New Paronellidae was divided into two subfamilies:Paronellinae(Paronellini+Cyphoderini+Bromacanthini)and Salininae(Cremastocephalini+Callyntrurini).Microfalculidae(Microfalcula)was closer to Salina and Akabosia and thus transferred into Cremastocephalini.This study erected a new classification framework for Entomobryoidea based upon comprehensive phylogenies.Chaetotaxic homologization across a wide range provided a standardized,comparable,powerful tool for taxonomy.
基金This work is supported by the National Institutes of Health(R01 HD10808 awarded to MDG).
文摘Male meiosis is a complex process whereby spermatocytes undergo cell division to form haploid cells.This review focuses on the role of retinoic acid(RA)in meiosis,as well as several processes regulated by RA before cell entry into meiosis that are critical for proper meiotic entry and completion.Here,we discuss RA metabolism in the testis as well as the roles of stimulated by retinoic acid gene 8(STRA8)and MEIOSIN,which are responsive to RA and are critical for meiosis.We assert that transcriptional regulation in the spermatogonia is critical for successful meiosis.
基金Supported by the Faculty of Medicine Siriraj Hospital,Mahidol University,No.(IO)R015731040。
文摘BACKGROUND This study aimed to explore clinical and molecular factors that cause discordance for clinical expression of Leber’s hereditary optic neuropathy(LHON)in a pair of identical twins with the 14484 point mutation.CASE SUMMARY Twin patients with the 14484 point mutation were studied for zygosity by using the Short Tandem Repeats Typing system.For the monozygotic twins,the radioactive restriction and densitometric analyses were used to quantitate the heteroplasmy level for the 14484 point mutation.The mitochondrial genome was analyzed to determine influential factors by mitochondrial deoxyribonucleic acid(DNA)sequencing,denaturing high-performance liquid chromatography and next generation sequencing.For the dizygotic twins,the nuclear DNA was analyzed.The twins with 14484 LHON were monozygotic with homoplasmy.No difference in the point mutation in mitochondrial DNA was found.No modifying genes that potentially influenced the disparity in phenotypic expression of LHON were detected in these twins.CONCLUSION This 11-year follow-up of monozygotic twins showed additional genetic modifications and epigenetic factors are possibly associated with discordance for LHON.
基金the World Climate Recruitment Programme’s (WCRP) Working Group on Coupled Modelling (WGCM)the Global Organization for Earth System Science Portals (GO-ESSP)+2 种基金jointly supported by the National Science Foundation of China (Grant Nos. 41991231, 91937302)the China 111 project (Grant No. B13045)supported by Supercomputing Center of Lanzhou University
文摘The measurement of atmospheric O_(2)concentrations and related oxygen budget have been used to estimate terrestrial and oceanic carbon uptake.However,a discrepancy remains in assessments of O_(2)exchange between ocean and atmosphere(i.e.air-sea O_(2)flux),which is one of the major contributors to uncertainties in the O_(2)-based estimations of the carbon uptake.Here,we explore the variability of air-sea O_(2)flux with the use of outputs from Coupled Model Intercomparison Project phase 6(CMIP6).The simulated air-sea O_(2)flux exhibits an obvious warming-induced upward trend(~1.49 Tmol yr−2)since the mid-1980s,accompanied by a strong decadal variability dominated by oceanic climate modes.We subsequently revise the O_(2)-based carbon uptakes in response to this changing air-sea O_(2)flux.Our results show that,for the 1990−2000 period,the averaged net ocean and land sinks are 2.10±0.43 and 1.14±0.52 GtC yr−1 respectively,overall consistent with estimates derived by the Global Carbon Project(GCP).An enhanced carbon uptake is found in both land and ocean after year 2000,reflecting the modification of carbon cycle under human activities.Results derived from CMIP5 simulations also investigated in the study allow for comparisons from which we can see the vital importance of oxygen dataset on carbon uptake estimations.
文摘Chemical modification of penicillin β-lactam ring was made.Six thiazolidine amides were produced through N4-C7 β-lactam ring opening of penicillin V methyl ester with various aliphatic,aromatic,and heterocyclic primary amines.Five 8-hydroxypenillic acid derivatives with side chains of methyl,propyl,benzyl,and diethylaminoethyl groups were yielded via β-lactam ring rearrangement from6-aminopenicillanic acid(6-APA).Parallel synthetic methods were used for the alkylation of8-hydroxypenillic acid and β-lactam ring opening of penicillin V methyl ester.The biological activities of the compounds were evaluated.
基金This work was supported by the National Institutes of Health,National Institute of Neurological Disorders and Stroke grant R01NS093314 as well as Small Business Innovation Research grant 1R43NS103596-01.
文摘Magnetic resonance imaging(MRI)is a clinically relevant,real-time imaging modality that is frequently utilized to assess stroke type and severity.However,specific MRI biomarkers that can be used to predict long-term functional recovery are still a critical need.Consequently,the present study sought to examine the prognostic value of commonly utilized MRI parameters to predict functional outcomes in a porcine model of ischemic stroke.Stroke was induced via permanent middle cerebral artery occlusion.At 24 hours post-stroke,MRI analysis revealed focal ischemic lesions,decreased diffusivity,hemispheric swelling,and white matter degradation.Functional deficits including behavioral abnormalities in open field and novel object exploration as well as spatiotemporal gait impairments were observed at 4 weeks post-stroke.Gaussian graphical models identified specific MRI outputs and functional recovery variables,including white matter integrity and gait performance,that exhibited strong conditional dependencies.Canonical correlation analysis revealed a prognostic relationship between lesion volume and white matter integrity and novel object exploration and gait performance.Consequently,these analyses may also have the potential of predicting patient recovery at chronic time points as pigs and humans share many anatomical similarities(e.g.,white matter composition)that have proven to be critical in ischemic stroke pathophysiology.The study was approved by the University of Georgia(UGA)Institutional Animal Care and Use Committee(IACUC;Protocol Number:A2014-07-021-Y3-A11 and 2018-01-029-Y1-A5)on November 22,2017.
文摘Enterococcus faecalis is a Gram-positive bacterium commonly found in the gastrointestinal tract that can cause serious infections. Many enterococci have broad resistance to antibiotics including penicillin, cephalosporins, aminoglycosides and glycopeptides. There are several adaptation mechanisms that bacteria can undergo to become more resistant, among them is the formation of biofilm. Several genes have been linked to the increase in the capacity of biofilm formation by bacteria such as gelE, esp and asa1. The aim of this research was to evaluate the biofilm formation of 12 E. faecalis isolates collected in hospitals and a standard strain, as well as to evaluate the hydrophobicity of its membrane and the presence of virulence genes. All the isolates formed biofilm and the characteristics of their membrane were variable. In addition, the presence of at least one virulence gene was found in all the 12 isolates, and none of the genes in the standard strain, indicating the acquisition of these genes in the hospital environment. With this, we can conclude that there is a close relationship between biofilm formation, acquisition of antibiotic resistance and the presence of virulence genes.
基金funded by the Research Council of Norway(GPS,AJ)the Swedish Research Council(FH,FE,AR)+1 种基金the University of Oslo(JSH)the Marie-Curie Foundation(FE)
文摘Background: Postzygotic isolation in the form of reduced viability and/or fertility of hybrids may help maintain species boundaries in the face of interspecific gene flow. Past hybridization events between house sparrows(Passer domesticus) and Spanish sparrows(P. hispaniolensis) have given rise to a homoploid hybrid species, the Italian sparrow(P. italiae). Although genetic incompatibilities are known to isolate these three species, the biological consequences of these incompatibilities are still unknown in early generation hybrids.Methods: We investigated whether F1 hybrids between house and Spanish sparrows experience reduced viability or fertility. More specifically, we generated hybrids through controlled crosses in aviaries, and compared ovaries of female hybrids with female of pure?species sparrows.Results: We found that overall, hybrid ovaries were underdeveloped and that half of all female hybrids exhibited symptoms of ovarian hypofunction(ovarian atrophy and complete absence of developed follicles).Conclusions: Fertility in hybrids is a common consequence or post?zygotic barriers between species. We discuss these results in light of previous findings on genetic incompatibilities between the parent species and the potential role of incompatibilities in hybrid speciation, a rare evolutionary process in birds.
文摘The influence of pollution from petroleum refining activities on the levels of nitrates and nitrites in five edible vegetable species was investigated. Besides, the kinetics of nitrite and nitrate was studied in vivo using albino rats with focus on the possible influence of concentration difference on kinetics and implications to toxicity. Leaf samples of the five vegetable species were collected randomly from various locations within Eleme, a host community of Port Harcourt Refinery Company and the Indorama Petrochemical Company. Also, samples were collected from Umuahia, which served as pollution-free control. The leaf samples were analyzed for their nitrite and nitrate contents. Nitrite was determined spectrophotometrically while nitrate was determined after cadmium column reduction. Results showed that samples from Eleme had higher mean nitrate (349.20 mg/100g dry leaf mass;P 0.05) as compared to the same samples from Umuahia. Solutions of nitrate and nitrite, equivalent in concentration to mean nitrate and nitrite content of the vegetable samples from the two locations were administered enterally to four groups of albino rats. Analysis of their blood levels were monitored five times at 30 minutes intervals following administration. Rates of change of blood nitrites and nitrates were found to be fairly constant in absorption as well as in the elimination phase. Their peak blood concentrations varied proportionately with their concentrations in administered solutions. However, peak blood nitrate was attained later in group of animals receiving higher amount of nitrate solution. Refining activities may pre-dispose people living within Eleme community to health hazards through contamination of edible vegetables.
基金National Institute of Health (S11 NS43499)RCMI (G12RR/AI03061, USA. )
文摘Lentiviral vectors have drawn considerable attention recently and show great promise to become important delivery vehicles for future gene transfer manipulation. In the present study we have optimized a protocol for preparation of human immunodeficiency virus type-1 (HIV-1)-based defective lentiviral vectors (DLV) and characterized these vectors in terms of their transduction of different cells. Transient co-transfection of 293T packaging cells with DNA plasmids encoding lentiviral vector constituents resulted in production of high-titer DLV (0.5-1.2 × 107IU/mL), which can be further concentrated over 100-fold through a single step ultracentrifugation. These vectors were capable of transducing a variety of cells from both primate and non-primate sources and high transduction efficiency was achieved using concentrated vectors. Assessment of potential generation of RCV revealed no detection of infection by infectious particles in DLV-transduced CEM, SupT-1 and MT-2 cells. Long-term culture of transduced cells showed a stable expression of transgenes without apparent alteration in cellular morphology and growth kinetics. Vector mobilization to untransduced cells mediated by wild-type HIV-1 infection was confirmed in this test. Challenge of transduced human T-lymphocytes with wild-type HIV-1 showed these cells are totally resistant to the viral infection. Considering the effective gene transfer and stable gene expression, safety and anti-HIV activity, these DLV vectors warrant further exploration for their potential use as a gene transfer vehicle in the development of gene therapy protocols.